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Biomedical subjects

J Gordon

Publications and source records attributed to J Gordon.

At least 271 records · Page 15Linked to original sources
PubMed1989

Monospermy and polyspermy after partial zona dissection of reinseminated human oocytes.

Partial zona dissection (PZD), a zona drilling method that uses mechanical force to open the zona pellucida while the oocyte is shrunken in a sucrose solution, was applied to 121 unfertilized 1-day-old mature human oocytes prior to reinsemination. The 115 surviving oocytes were divided into three groups in which the duration between sucrose addition and reinsemination was varied: I) Less than 20 minutes, II) 21 to 45 minutes, and III) longer than 45 minutes. There was a trend toward a reduced fertilization and polyspermy rate as the time between sucrose exposure and insemination in sucrose-free medium increased. Moreover, there was a statistically significant reduction in the number of oocytes penetrated by more than four sperm in group III (0/41) versus group I (7/34), and in group III, parthenogenetic development was observed. The incidence of polyspermy was also increased in oocytes manipulated more than 25 hours after retrieval compared with those manipulated 21-24 hours after recovery, supporting the idea that aged oocytes have a reduced ability to block polyspermy. Oocyte contraction in sucrose occurred in three different patterns: spherical, pear-shaped, and crenated. Both the fertilization and polyspermy rates were significantly higher in the crenated group. These results indicate that changes resembling activation occur following sucrose exposure and that sucrose activation can be used to reduce the risk of polyspermic fertilization in zona drilling procedures. In addition, the pattern of shrinkage in sucrose can be used as an indicator of oocyte receptivity to sperm penetration.

Cell Membrane↗
PubMed1989

B cell dependent T cell function blocked by perinatal exposure of mice to anti-IgM antibodies.

Mice born to mothers deprived of B lymphocytes by their chronic treatment with anti-IgM antibodies (Su/N) do not possess naturally occurring anti-ids (present in sera of normal mice at 2 weeks of age) up to 10 weeks, despite the presence of normal levels of B cells and serum Ig (in these animals). Su/N mice of the same age also lack a T cell subset which together with anti-ids are thought to participate in an antisuppressor regulatory pathway. It is suggested that early development of these T cells may be linked and be dependent on the presence of these anti-ids synthesized early in ontogeny, providing one explanation for a selective T cell deficiency of B cell-deprived mice.

Animals↗
PubMed1989

CD23: a multi-functional receptor/lymphokine?

With the demonstration of identity between CD23 and the low affinity IgE Fc receptor (Fc epsilon RII), two previously separate avenues of immunological research have converged into one. Particularly in its guise as 'Blast-2' antigen, evidence has been mounting to implicate CD23 as an important molecule in B-cell growth regulation. It might seem pertinent, however, to question a role for an apparently isotype-specific immunoglobulin (Ig) receptor in general B-cell processes. In this article, John Gordon and colleagues attempt to reconcile the two, currently diverse, schools of thought regarding the primary function of CD23 and to provide a structural model that accounts for the biological pleiotropy observed.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

Estimating mortality risk in preoperative patients using immunologic, nutritional, and acute-phase response variables.

We measured the delayed type hypersensitivity (DTH) skin test response, along with additional variables of host immunocompetence in 245 preoperative patients to determine which variables are associated with septic-related deaths following operation. Of the 14 deaths (5.7%), 12 were related to sepsis and in 2 sepsis was contributory. The DTH response (p less than 0.00001), age (p less than 0.0002), serum albumin (p less than 0.003), hemoglobin (p less than 0.02), and total hemolytic complement (p less than 0.03), were significantly different between those who died and those who lived. By logistic regression analysis, only the DTH skin test response (log likelihood = 41.7, improvement X2 = 6.24, p less than 0.012) and the serum albumin (log likelihood = 44.8, improvement X2 = 17.7, p less than 0.001) were significantly and independently associated with the deaths. The resultant probability of mortality calculation equation was tested in a separate validation group of 519 patients (mortality = 5%) and yielded a good predictive capability as assessed by (1) X2 = 0.08 between observed and expected deaths, NS; (2) Goodman-Kruskall G statistic = 0.673) Receiver-Operating-Characteristic (ROC) curve analysis with an area under the ROC curve, Az = 0.79 +/- 0.05. We conclude that a reduced immune response (DTH skin test anergy) plus a nutritional deficit and/or acute-phase response change are both associated with increased septic-related deaths in elective surgical patients.

Acute-Phase Proteins↗
PubMed1989

Indications for barium enema preceding colostomy closure in trauma patients.

The need for a barium enema (BE) preceding colostomy closure is controversial. In the process of evaluating the usefulness of BE before closure of colostomies performed for colorectal injuries, we reviewed our experience with 84 trauma patients who underwent BE before colostomy closure. Patients who had their colonic injuries repaired or diverted during the initial procedure did not benefit from the precolostomy closure contrast study. In this group of patients artifacts on BE had to be ruled out by endoscopy or repeat radiography in 9.5% of patients. Barium enema was found beneficial in evaluating colorectal injuries below the peritoneal reflection in one out of 20 patients. However, since the rectal injuries are not usually explored and repaired during the initial procedure, investigation by endoscopy and contrast studies may still be indicated preceding colostomy closure.

Adolescent↗
PubMed1989

B-cell reconstitution after autologous bone marrow transplantation: increase in serum CD23 ("IgE-binding factor") precedes IgE and B-cell regeneration.

The serum levels of IgE and the soluble cleavage product of CD23 (sCD23) were prospectively monitored for up to 1 year after transplantation in 34 patients who underwent autologous (n = 33) or syngeneic (n = 1) bone marrow transplantation (BMT). In 25 patients (74%), a transient IgE peak (two- to 2,750-fold increase) appeared in the serum 3 to 4 weeks after BMT. In 18 patients (51%), a two- to 125-fold increase in sCD23 coincided with the IgE peak. In only three patients was a sCD23 peak observed without a concomitant increase in IgE. The sCD23 increment preceded the IgE peak in each individual case. During the period of increased sCD23 serum levels, the absolute numbers of circulating B cells and other cell types expressing surface CD23 were extremely low. The biologic significance of these findings is discussed in light of present knowledge of regulation of B-cell growth and differentiation with special reference to the role of sCD23 as a multifunctional cytokine.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

Regulation of resting and cycling human B lymphocytes via surface IgM and the accessory molecules interleukin-4, CD23 and CD40.

Experiments were designed in order to compare directly the ability of a new and potent monoclonal anti-mu chain antibody to initiate or maintain stimulation in resting and cycling B lymphocytes, respectively. Resting B cells could be stimulated by soluble anti-mu only in the presence of additional signals; these could be supplied by a high dose of phorbol ester or a combination of interleukin-4 (IL-4) and the CD40 antibody, G28-5. Immobilization of anti-mu not only increased the magnitude of the resting B-cell response but also diminished the co-factor requirements. The 'background' stimulation obtained when using a high concentration of immobilized anti-mu was unexpectedly reduced in the presence of IL-4 alone. The duration, but not the magnitude, of the IL-4 signal required for promoting optimal responses varied with the co-stimulation applied. Importantly, the threshold concentrations of soluble anti-mu needed to trigger the resting B cells were reduced upon the addition of each co-stimulant. With actively cycling B cells, both soluble and immobilized anti-mu were now capable of sustaining stimulation which could be prolonged on the addition of IL-4 and/or G28-5. In both resting and cycling populations, a strong correlation was noted between the magnitude of stimulation elicited when IL-4 was present and the release of the soluble CD23 molecule. Moreover, IL-4-promoted, but not other, stimulations could be augmented up to 10-fold by the inclusion of the CD23 antibody MHM6. Both the resting and cycling B-cell populations were found to secrete IgM in direct response to IL-4 and G28-5; this factor-driven production of IgM was differentially modulated by soluble and immobilized anti-mu in the two populations.

Antibodies, Monoclonal↗
PubMed1989

Soluble fragments of the low-affinity IgE receptor (CD23) inhibit the spontaneous migration of U937 monocytic cells: neutralization of MIF-activity by a CD23 antibody.

U937 monocytic cells were found to respond by diminished spontaneous migration when confronted with affinity-purified soluble fragments of the low-affinity receptor for IgE (FcER2/CD23). Unlike B lymphoma cells, U937 cells could not be activated to respond with enhanced DNA synthesis through their membrane-bound CD23 antigen by MHM6, a monoclonal antibody within the CD23 cluster. MHM6 did, however, effectively neutralize the U937-directed MIF (migration inhibition factor) activity contained within the soluble CD23 preparations. The findings not only suggest a role for soluble CD23 as a novel cytokine at sites of inflammation but also indicate different functions for the membrane-bound forms expressed on B cells and monocytes.

Antibodies, Monoclonal↗
PubMed1989

Immunoblotting in the clinical laboratory.

Since its introduction in 1979 protein blotting has become a routine tool in research laboratories. In the clinical laboratory its potential is becoming recognised for applications in fields such as infectious and autoimmune diseases, allergy and others. In this article we would like to outline the basic principles of protein blotting, to illustrate these with some examples related to clinical applications and to point out differences between these and classical methods.

Allergens↗
PubMed1989

Phorbol ester and calcium ionophore are sufficient to promote cell replication in cultures of quiescent human B lymphocytes.

Highly purified, resting B cells could be induced to grow for up to 10 days by culturing in the presence of a synergistic combination of a tumour-promoting phorbol ester and the calcium ionophore ionomycin. In spite of evident cell death occurring, four to five times as many viable B lymphocytes could be harvested at the end of culture than were initially plated. Soluble factors derived from T cells (interleukin-2, commercial B-cell growth factor) or monocytes (interleukin-1) failed to augment further the growth-promotion observed. Evidence is presented to suggest that an autocrine component might be necessary for maintenance of the cell-cycle and growth initiated by the phorbol ester and calcium ionophore combination. The significance of these findings to B-cell physiology are discussed.

B-Lymphocytes↗
PubMed1989

Tests of two new polyurethane foam wheelchair tires.

The performance characteristics of four 24-inch wheelchair tires are considered; one pneumatic and three airless. Specifically, two new airless polyurethane foam tires (circular and tapered cross-section) were compared to both a molded polyisoprene tire and a rubber pneumatic tire. Rolling resistance, coefficient of static friction, spring rate, tire roll-off, impact absorption, wear resistance, and resistance to compression set were the characteristics considered for the basis of comparison. Although the pneumatic tire is preferred by many wheelchair users, the two new polyurethane foam tires were found to offer a performance similar to the high-pressure pneumatic tire. In addition, the foam tires are less expensive and lighter in weight than the other tires tested.

Equipment Design↗
PubMed1988

Resting B lymphocytes can be triggered directly through the CDw40 (Bp50) antigen. A comparison with IL-4-mediated signaling.

Resting tonsillar B lymphocytes were shown to enlarge and become more buoyant when exposed to either IL-4 or a mAb (G28-5) to the 50-kDa CDw40 Ag. A striking feature of activation through CDw40 was the promotion of strong homotypic adhesions which did not occur in populations cultured with IL-4. Whereas the CDw40 antibody down-regulated its target Ag, an increased expression of CDw40 accompanied IL-4 stimulation. Similarly, only IL-4, and not the CDw40 antibody, was able to induce the appearance of CD23 on the resting B cell surface. Functionally, the major consequence of ligating CDw40 on resting B cells was that they remained alert to subsequent mitogenic signaling--cells incubated with IL-4 developed the same sluggish response as noted in control cultures. Together, IL-4 and the CDw40 antibody provoked a small, but significant, level of DNA synthesis in tonsillar B cells which was enhanced dramatically by the inclusion of low m.w. B cell growth factor. This latter agent had no discernible direct effect on resting B lymphocytes. The different pathways which have been observed for triggering resting B cells are discussed.

Antibodies, Monoclonal↗
PubMed1988

Quantitative and qualitative study of the restoration by cytokines of mononuclear cell delivery to skin test sites in anergic surgical patients.

We tested the hypothesis that anergy is associated with reduced delivery of mononuclear cells (MNCs) to delayed-type hypersensitivity sites and that cytokine (CK)-rich supernatants from mixed lymphocyte cultures overcome the defect. Significantly fewer MNCs were delivered to skin window chambers placed over purified protein derivative (PPD) injection sites of previously sensitized anergic patients compared with hospitalized PPD-reactive patients; coinjection of CK with PPD restored the MNC delivery in anergic patients to normal levels. The T cells cloned from a PPD + CK site of an anergic patient consisted of CD4+ and CD8+ cells whose capacities included cytotoxicity and lymphokine production. The frequency of PPD-reactive cells was 15 times greater than in the blood. Thus, the restoration by CK of the delivery of antigen-specific cells capable of participating in cell-mediated immunity in anergic patients may be feasible.

Adult↗
PubMed1988

Lack of cytokine-induced skin reaction correlates with acute physiology score and mortality in patients receiving intensive care.

Because the majority of patients receiving intensive care are anergic to ubiquitous skin test antigens, prediction of clinical outcome cannot be based on their delayed-type hypersensitivity score, which is 0, but which is also a strong indicator of sepsis-related mortality in the preoperative patient. However, a cytokine-rich supernatant generated in the mixed lymphocyte culture reaction is able to induce an early skin reaction that peaks at 12 hours and wanes by 24 hours in some, but not all, anergic patients. Assessment of the clinical course of these patients demonstrated that only three of 25 patients who had a skin reaction larger than 5 mm died, compared with ten of 16 patients who failed to display this early reaction. Further analysis showed that both the cytokine-induced reaction and the acute physiology score significantly and independently contributed to the probability of death in anergic patients. These data suggest that the ability to generate a local inflammatory response to cytokines in anergic patients identifies a subpopulation of patients who have maintained some host-defense responsiveness and this response can be utilized to predict outcome.

Acute Disease↗